Smooth Muscle Cell Phenotypic Diversity

Abstract

Vascular smooth muscle cells (SMC) play a critical role in controlling blood pressure and blood distribution, as well as maintaining the structural integrity of the blood vessel. SMC also participate in physiological and pathological vascular remodeling due to their remarkable ability to dynamically modulate their phenotype. During the past decade, the development of in vivo fate mapping systems for unbiased identification and tracking of SMC and their progeny has led to major discoveries as well as the reevaluation of well-established concepts about the contribution of vascular SMC in major vascular diseases including atherosclerosis. Lineage tracing studies revealed that SMC undergoes multiple phenotypic transitions characterized by the expression of markers of alternative cell types (eg, macrophage-like and mesenchymal-stem cell-like) and populate injured or diseased vessels by oligoclonal expansion of a limited number of medial SMC. With the development of high-throughput transcriptomics and single-cell RNA sequencing (scRNAseq), the field is moving forward towards in-depth SMC phenotypic characterization. Herein, we review the major observations put forth by lineage and clonality tracing studies and the evidence in support for SMC phenotypic diversity in healthy and diseased vascular tissue. We will also discuss the opportunities and remaining challenges of combining lineage tracing and single-cell transcriptomics technologies, as well as studying the functional relevance of SMC phenotypic transitions and identifying the mechanisms controlling them.

Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker

“…Thus, we tested whether hsa_circ_0001445 may have similar behavior in coronary atherosclerotic conditions. Supporting our previous findings, an atherogenic environment promoted the unloading of hsa_circ_0001445 into the extracellular vesicles secreted by coronary SMCs, the main cellular type in the vascular wall and a key player in coronary atherosclerosis development . These results are noteworthy since a biomarker of CAD should reflect the pathological processes occurring in the coronary artery wall.…”

“…Supporting our previous findings, an atherogenic environment promoted the unloading of hsa_ circ_0001445 into the extracellular vesicles secreted by coronary SMCs, the main cellular type in the vascular wall and a key player in coronary atherosclerosis development. 46 These results are noteworthy since a biomarker of CAD should reflect the pathological processes occurring in the coronary artery wall. At this point, hsa_circ_0001445 may, therefore, be considered a reported biomarker of CAD.…”

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

“…In a post-genomic era, information-rich technologies are proving critically important drivers for both fundamental biology and personalised medicine 37 . In particular, scRNA-seq clustering has elucidated cell-to-cell heterogeneity and uncovered cell subgroups and cell dynamics in numerous systems 38 , including vascular 21,22,39 . Label-free technologies for bioanalytical applications have also attracted recent attention with several different classes of label-free sensor detectors now being developed, including plasmonic, photonic, electrical and mechanical sensors 40 .…”

“…There was a significant increase in the fraction of Cnn1 and Myh11 positive cells in TGF-β1 treated cells [ Figure 4B] concomitant with a significant increase in the enrichment of the SMC epigenetic histone mark, di-methylation of lysine 3 on Histone 4 (H3K4me2) 39 and a decrease in the repressive mark, tri-methylation of lysine 27 on Histone 3 (H3K27me3) 50 at the Myh11 locus [ Figure 4C]. The expression of Cnn1 and Myh11 was also increased in protein lysates following with TGF-β1 treatment [ Figure 4D].…”

Decoding the transcriptome of atherosclerotic plaque at single-cell resolution

“…The pathophysiology of atherosclerosis is exceptionally complex and involves inflammation 1 , cellular transdifferentiation 2,3 , and dynamic interactions between a variety of cell types within the vascular wall 4,5 . For example, the phenotypic landscape of VSMCs is increasingly understood to be quite dynamic as these cells often participate in phenotype switching 6 and contribute to the development of extracellular matrix producing cells in atherosclerosis 4 . Many of these pathogenic processes are mediated through molecular crosstalk between VSMCs 7 , however disease progression in general is increasingly appreciated to involve coordinated genomic and molecular communication between the plethora of immune cell subtypes and other cellular components of the arterial wall 8,9 .…”